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Gregory A. Petsko (born August 7, 1948) is an American biochemist and member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society. He is currently Professor of Neurology at the Ann Romney Center for Neurologic Diseases at Harvard Medical School and Brigham and Women's Hospital. He formerly had an endowed professorship (the Arthur J. Mahon Chair) in Neurology and Neuroscience at Weill Cornell Medical College and is still an adjunct professor of Biomedical Engineering at Cornell University, and is also the Gyula and Katica Tauber Professor, Emeritus, in biochemistry and chemistry at Brandeis University. On October 24, 2023, in a ceremony in the East Room of the White House, President Joe Biden presented Gregory Petsko and eight others with the National Medal of Science, the highest honor the United States can bestow on a scientist and engineer.

Greg Petsko
Born (1948-08-07) August 7, 1948 (age 76)
EducationPrinceton University (BS)
Merton College, Oxford (MS, PhD)
SpouseLaurie Glimcher[1]
AwardsRhodes Scholarship
Member of the U.S. National Academy of Sciences
Member of the U.S. National Academy of Medicine
Member of the American Academy of Arts and Sciences
Member of the American Philosophical Society
Scientific career
InstitutionsHarvard Medical School
Brigham and Women's Hospital
Weill Cornell Medical College
Cornell University
Brandeis University
Wayne State University School of Medicine
MIT
Max Planck Institute
University of Oxford
Princeton University
ThesisStructural studies of triose phosphate isomerase. (1974)
Doctoral advisorDavid Chilton Phillips
WebsiteOfficial website

As of 2020 Petsko's research interests are understanding the biochemical bases of neurological diseases like Alzheimer's, Parkinson's, and ALS, discovering drugs (especially by using structure-based drug design) and biologics, especially gene therapy, that could therapeutically affect those biochemical targets, and seeing any resulting clinical candidates tested in humans. He has made key contributions to the fields of protein crystallography, biochemistry, biophysics, enzymology, and neuroscience.

Education

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Petsko was an undergraduate at Princeton University, where he graduated summa cum laude in 1970. He received a Rhodes Scholarship, and obtained his doctorate in Molecular Biophysics from Merton College, Oxford supervised by David Phillips, studying the structure and mechanism of the enzyme triosephosphate isomerase. [1]

He did a brief postdoctoral fellowship in Paris with Pierre Douzou, studying enzymology at low temperatures. In 1996 he did a sabbatical at the University of California at San Francisco with Ira Herskowitz, where he learned yeast genetics and molecular biology with the support of a Guggenheim Foundation Fellowship.[2]

Career

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President Joe Biden awards the National Medal of Science to Professor Gregory A. Petsko of Harvard Medical School and Brigham & Women's Hospital on October 24, 2023. Photo by Jay Premack/USPTO.

Petsko's independent academic career has included stints at Wayne State University School of Medicine, the Massachusetts Institute of Technology, the Max Planck Institute for Medical Research in Heidelberg, and, from 1991 until 2012, Brandeis University, where he was Professor of Biochemistry and of Chemistry and director of the Rosenstiel Basic Medical Sciences Research Center. He is past-president of the American Society for Biochemistry and Molecular Biology and of the International Union of Biochemistry and Molecular Biology. He is an elected member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. He is a foreign member of the Hungarian Academy of Sciences and has an honorary Doctor of Laws from Dalhousie University. In April 2010, he was elected to the American Philosophical Society.[2] In 2012, he announced that he was moving to Weill Cornell Medical College in New York City, where his wife, the world-renowned immunologist Dr. Laurie Glimcher, had been appointed dean.[3] He was appointed at Weill Cornell Medical College as the director of the Helen and Robert Appel Alzheimer's Disease Research Institute and the Arthur J. Mahon Professor of Neurology and Neuroscience in the Feil Family Brain and Mind Research Institute, and at Cornell University as adjunct professor of Biomedical Engineering, and retained an appointment at Brandeis University as Gyula and Katica Tauber Professor of Biochemistry and Chemistry, Emeritus.[4][5] His wife was named president and CEO of the Dana–Farber Cancer Institute in October 2016, and in January 2019 he followed her back to Boston, assuming his present position as Professor of Neurology at the Ann Romney Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School. On October 24, 2023, he and eight other scientists received the National Medal of Science from President Joe Biden. The National Medal of Science is the highest honor the United States can confer on a scientist; since the first was awarded in 1963 by President John F. Kennedy, only 506 individuals have received it.[3][4][5][6]

Research

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Petsko's current research interests are understanding the biochemical bases of neurological diseases like Alzheimer's, Parkinson's, and ALS, discovering drugs (especially by using structure-based drug design) that could therapeutically affect those biochemical targets, and seeing any resulting drug and gene therapy candidates tested in humans.[5][6]

Petsko's past research interests[7] have been in protein crystallography and enzymology. He is co-author with Dagmar Ringe of Protein Structure and Function.[8] He was also the author of a monthly column in Genome Biology[9][10] modelled after an amusing column in Current Biology penned by Sydney Brenner.[11] The first ten years of that column are available as an eBook.[12]

Petsko is best known for his collaborative work with Dagmar Ringe, in which they used X-ray crystallography to solve important problems in protein function including protein dynamics as a function of temperature and problems in mechanistic enzymology,[13][14][15] and for his collaborative work with Dr. Scott Small of Columbia University, which focuses on the retromer endosomal protein trafficking pathway and its role in Alzheimer's and Parkinson's diseases.[16][17][18][19][20][21][22][23][24]

At MIT and Brandeis, he and Dagmar Ringe trained a large number of current leaders in structural molecular biology who now have leadership roles in science. These individuals include:

References

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  1. ^ Bailey, Melissa (2016-03-01). "Recruited to lead Harvard med, 'fearless' scientist chose Dana-Farber". STAT. Retrieved 2023-01-02.
  2. ^ "Biochemist Greg Petsko elected to American Philosophical Society".
  3. ^ Tate Herbert for The Justice November 13, 2012 Petsko set to leave University for New York City in 2014
  4. ^ Weill Cornell Newsroom. April 16, 2014 No Stone Unturned: Interview with Gregory Petsko
  5. ^ a b Petsko Laboratory Homepage
  6. ^ Columbia University Newsroom. April 20, 2014 'Chaperone' compounds offer new approach to Alzheimer's treatment
  7. ^ Gregory Petsko publications indexed by Microsoft Academic
  8. ^ Petsko, Gregory A. (2008). Protein Structure and Function (Primers in Biology). Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-955684-7.
  9. ^ Petsko, G. A. (2010). "A Faustian bargain". Genome Biology. 11 (10): 138. doi:10.1186/gb-2010-11-10-138. PMC 3218652. PMID 21062515.
  10. ^ Petsko, G. A. (2011). "Food of the dogs". Genome Biology. 12 (7): 122. doi:10.1186/gb-2011-12-7-122. PMC 3218821. PMID 21787380.
  11. ^ Brenner, S. (2002). "The worm's turn". Current Biology. 12 (21): R713. Bibcode:2002CBio...12.R713B. doi:10.1016/s0960-9822(02)01241-1. PMID 12419193.
  12. ^ Petsko, Gregory (2010-10-10). Gregory Petsko in Genome Biology: The first 10 years. BioMed Central.
  13. ^ Frauenfelder, H.; Petsko, G. A.; Tsernoglou, D. (1979). "Temperature-dependent X-ray diffraction as a probe of protein structural dynamics". Nature. 280 (5723): 558–563. Bibcode:1979Natur.280..558F. doi:10.1038/280558a0. PMID 460437. S2CID 4280206.
  14. ^ Schlichting, I.; Berendzen, J.; Chu, K.; Stock, A. M.; Maves, S. A.; Benson, D. E.; Sweet, R. M.; Ringe, D.; Petsko, G. A.; Sligar, S. G. (2000). "The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution". Science. 287 (5458): 1615–1622. Bibcode:2000Sci...287.1615S. doi:10.1126/science.287.5458.1615. PMID 10698731.
  15. ^ Karplus, M.; Petsko, G. A. (1990). "Molecular dynamics simulations in biology". Nature. 347 (6294): 631–639. Bibcode:1990Natur.347..631K. doi:10.1038/347631a0. PMID 2215695. S2CID 6143542.
  16. ^ Young, Jessica E.; Holstege, Henne; Andersen, Olav M.; Petsko, Gregory A.; Small, Scott A. (2023). "On the causal role of retromer-dependent endosomal recycling in Alzheimer's disease". Nature Cell Biology. 25 (10): 1394–1397. doi:10.1038/s41556-023-01245-2. ISSN 1465-7392. PMC 10788784. PMID 37803174. S2CID 263741870.
  17. ^ Jensen, Anne Mette G.; Kitago, Yu; Fazeli, Elnaz; Vægter, Christian B.; Small, Scott A.; Petsko, Gregory A.; Andersen, Olav M. (2023-01-24). "Dimerization of the Alzheimer's disease pathogenic receptor SORLA regulates its association with retromer". Proceedings of the National Academy of Sciences. 120 (4): e2212180120. Bibcode:2023PNAS..12012180J. doi:10.1073/pnas.2212180120. ISSN 0027-8424. PMC 9942828. PMID 36652482.
  18. ^ Qureshi, Yasir H.; Berman, Diego E.; Marsh, Samuel E.; Klein, Ronald L.; Patel, Vivek M.; Simoes, Sabrina; Kannan, Suvarnambiga; Petsko, Gregory A.; Stevens, Beth; Small, Scott A. (2022). "The neuronal retromer can regulate both neuronal and microglial phenotypes of Alzheimer's disease". Cell Reports. 38 (3): 110262. doi:10.1016/j.celrep.2021.110262. PMC 8830374. PMID 35045281.
  19. ^ Small, Scott A.; Petsko, Gregory A. (2020-12-02). "Endosomal recycling reconciles the Alzheimer's disease paradox". Science Translational Medicine. 12 (572). doi:10.1126/scitranslmed.abb1717. ISSN 1946-6234. PMC 8025181. PMID 33268506.
  20. ^ Petsko, Gregory A.; Small, Scott A. (2022). "Elucidating the causes of neurodegeneration". Science. 377 (6601): 31–32. Bibcode:2022Sci...377...31P. doi:10.1126/science.adc9969. ISSN 0036-8075. PMID 35771902. S2CID 250175089.
  21. ^ Young, Jessica E.; Fong, Lauren K.; Frankowski, Harald; Petsko, Gregory A.; Small, Scott A.; Goldstein, Lawrence S.B. (2018). "Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein". Stem Cell Reports. 10 (3): 1046–1058. doi:10.1016/j.stemcr.2018.01.031. PMC 5919412. PMID 29503090.
  22. ^ Small, Scott A.; Simoes-Spassov, Sabrina; Mayeux, Richard; Petsko, Gregory A. (2017). "Endosomal Traffic Jams Represent a Pathogenic Hub and Therapeutic Target in Alzheimer's Disease". Trends in Neurosciences. 40 (10): 592–602. doi:10.1016/j.tins.2017.08.003. PMC 5654621. PMID 28962801.
  23. ^ Small, Scott A.; Petsko, Gregory A. (2015). "Retromer in Alzheimer disease, Parkinson disease and other neurological disorders". Nature Reviews Neuroscience. 16 (3): 126–132. doi:10.1038/nrn3896. ISSN 1471-003X. PMID 25669742. S2CID 5166260.
  24. ^ Mecozzi, Vincent J; Berman, Diego E; Simoes, Sabrina; Vetanovetz, Chris; Awal, Mehraj R; Patel, Vivek M; Schneider, Remy T; Petsko, Gregory A; Ringe, Dagmar; Small, Scott A (2014). "Pharmacological chaperones stabilize retromer to limit APP processing". Nature Chemical Biology. 10 (6): 443–449. doi:10.1038/nchembio.1508. ISSN 1552-4450. PMC 4076047. PMID 24747528.